Linking Asymmetric Cell Division to the Terminal Differentiation Program of Postmitotic Neurons in C. elegans

被引:70
作者
Bertrand, Vincent [1 ]
Hobert, Oliver [1 ]
机构
[1] Columbia Univ, Med Ctr, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA
基金
美国国家卫生研究院;
关键词
CIS-REGULATORY ARCHITECTURE; CENTRAL-NERVOUS-SYSTEM; LIM-HOMEOBOX GENE; CAENORHABDITIS-ELEGANS; BETA-CATENIN; RECIPROCAL ASYMMETRY; FATE SPECIFICATION; ZIC GENES; PROTEIN; POP-1;
D O I
10.1016/j.devcel.2009.02.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
How asymmetric divisions are connected to the terminal differentiation program of neuronal subtypes is poorly understood. In C. elegans, two homeodomain transcription factors, TTX-3 (a LHX2/9 ortholog) and CEH-10 (a CHX10 ortholog), directly activate a large battery of terminal differentiation genes in the cholinergic interneuron AIY. We establish here a transcriptional cascade linking asymmetric division to this differentiation program. A transient lineage-specific input formed by the Zic factor REF-2 and the bHLH factor HLH-2 directly activates ttx-3 expression in the AN mother. During the terminal division of the AIY mother, an asymmetric Wnt/beta-catenin pathway cooperates with TTX-3 to directly restrict ceh-10 expression to only one of the two daughter cells. TTX-3 and CEH-10 automaintain their expression, thereby locking in the differentiation state. Our study establishes how transient lineage and asymmetric division inputs are integrated and suggests that the Wnt/beta-catenin pathway is widely used to control the identity of neuronal lineages.
引用
收藏
页码:563 / 575
页数:13
相关论文
共 55 条
[1]  
Alper S, 2002, DEVELOPMENT, V129, P3335
[2]  
Altun-Gultekin Z, 2001, DEVELOPMENT, V128, P1951
[3]   Wnt signaling and a Hox protein cooperatively regulate PSA-3/Meis to determine daughter cell fate after asymmetric cell division in C-elegans [J].
Arata, Yukinobu ;
Kouike, Hiroko ;
Zhang, Yanping ;
Herman, Michael A. ;
Okano, Hideyuki ;
Sawa, Hitoshi .
DEVELOPMENTAL CELL, 2006, 11 (01) :105-115
[4]   The role of Zic genes in neural development [J].
Aruga, J .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2004, 26 (02) :205-221
[5]   The homeobox genes Lhx7 and Gbx1 are expressed in the basal forebrain cholinergic system [J].
Asbreuk, CHJ ;
Van Schaick, HSA ;
Cox, JJ ;
Kromkamp, M ;
Smidt, MP ;
Burbach, JPH .
NEUROSCIENCE, 2002, 109 (02) :287-298
[6]   A posterior centre establishes and maintains polarity of the Caenorhabditis elegans embryo by a Wnt-dependent relay mechanism [J].
Bischoff, Marcus ;
Schnabel, Ralf .
PLOS BIOLOGY, 2006, 4 (12) :2262-2273
[7]   Regulatory gene networks and the properties of the developmental process [J].
Davidson, EH ;
McCay, DR ;
Hood, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (04) :1475-1480
[8]   Neural stem cells: balancing self-renewal with differentiation [J].
Doe, Chris Q. .
DEVELOPMENT, 2008, 135 (09) :1575-1587
[9]   Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation [J].
Ebert, PJ ;
Timmer, JR ;
Nakada, Y ;
Helms, AW ;
Parab, PB ;
Liu, Y ;
Hunsaker, TL ;
Johnson, JE .
DEVELOPMENT, 2003, 130 (09) :1949-1959
[10]   The molecular signature and cis-regulatory architecture of a C-elegans gustatory neuron [J].
Etchberger, John F. ;
Lorch, Adam ;
Sleumer, Monica C. ;
Zapf, Richard ;
Jones, Steven J. ;
Marra, Marco A. ;
Holt, Robert A. ;
Moerman, Donald G. ;
Hobert, Oliver .
GENES & DEVELOPMENT, 2007, 21 (13) :1653-1674